Major neuropsychiatric disorders such as Alzheimer?s disease, Parkinson?s disease, schizophrenia and depression are associated with and in some cases caused by chemical imbalances in the brain. The purpose of this research is to develop probes that can be used to assess these chemical imbalances so as to better understand these disorders and hopefully to improve their treatments. A major goal of the Molecular Imaging Branch is to develop new radiotracers and new imaging paradigms to study abnormal protein targets in patients with several neuropsychiatric disorders. The purpose of this research is to evaluate in vivo the pharmacokinetics, sensitivity and reproducibility of brain imaging measurements of radiolabeled probes for use in positron emission tomography (PET). Animals will be used to evaluate new tracers and new methods (e.g., combined with a pharmacological challenge) prior to their use in human subjects. Testing of these tracers in animals prior to their extension to humans is essential to ensure the validity of the measurement and the safety of the procedures. During the prior year (October 2001 ? September 2002), we initiated two studies. 1) PET imaging in mice. A new state-of-the-art PET camera was built in-house at NIH by Mike Green and became operational about 6 months ago. We have worked with Mr. Green to make the camera operational for imaging of mice. Specifically, we implemented appropriate animal handling procedures, methods for injection of radiotracer and image acquisition, and means for computer-assisted quantitative analysis of the resulting images. We expect to use these methods over the coming year in a transgenic mouse model of Alzheimer's disease to evaluate new probes for amyloid, a protein that accumulates in the brain and kills neurons. 2) Monkey imaging of a probe for the serotonin transporter. We have evaluated a new PET probe for the serotonin transporter, the target site of the most commonly used antidepressant medications. We have determined that this radiotracer is well tolerated in monkeys and gives a safe level of radiation exposure. With this information, we will be able to extend the use of this tracer to human subjects in the coming year.